Alfentanil vs Fentanyl Onset

The onset of intravenous narcotic medications (morphine, fentanyl, remifentanil, alfentanil, sufentanil, etc.) is related to their respective lipid solubilities. For example, fentanyl is roughly 600x more lipid soluble than morphine, and therefore has a much faster onset. However, alfentanil is an exception to the rule… and exams love to torture is with exceptions. 😉

Although fentanyl is 6x more lipid soluble than alfentanil, the latter has a faster onset. Why? 90% of alfentanil is unionized at physiologic pH compared to only 10% of fentanyl. It’s this unionized fraction of drug which more readily traverses lipid membranes to confer analgesic effects in the central nervous system.

Additionally, the volume of distribution of alfentanil is about 25% of that of fentanyl, so all things being equal, more of the drug remains in the blood to exert its effects. This also explains why alfentanil is cleared quicker than fentanyl.

Because of the quick onset/offset of alfentanil, it’s exceptionally useful for brief but intense periods of stimulation (ie, placing the skull in Mayfield pins). 🙂